胸苷酸合成酶基因多态性与肺癌易感性关系

Association between thymidylate synthase gene polymorphism and lung cancer susceptibility

目的探讨胸苷酸合成酶(TS)基因多态性与肺癌易感性的关系。方法应用聚合酶链式反应(PCR)方法检测青岛地区原发性肺癌患者473例及健康对照641人的TS 5’-非翻译区(untranslated region,UTR)多态性分布,以非条件logistic回归模型分析TS基因多态性与肺癌易感性的关系。结果 TS 5’-UTR的3种基因型3R/3R、2R/3R、2R/2R在病例组的频率分别为62.2%、34.0%和3.8%,在对照组中则分别为60.5%、37.0%和2.5%,分布差异无统计学意义(P>0.05);以携带TS 5’-UTR 3R/3R基因型者为参照,携带TS 5’-UTR 2R/3R基因型者发生肺癌的风险减少,OR值为0.90(95%CI=0.69～1.17),而携带TS 5’-UTR 2R/2R基因型者发生肺癌风险增加,OR值为1.64(95%CI=0.80～3.38),但差异均无统计学意义(P>0.05);以性别、年龄、吸烟、饮酒、病理类型,临床分期分层分析结果表明,TS 5’-UTR基因多态性与肺癌易感性无明显关联(均P>0.05)。结论 TS 5’-UTR多态与肺癌易感性无显著关联,未发现该基因多态性与吸烟、饮酒存在明显的交互作用。

Objective To study the relationship between the polymorphism in the 5＇-untranslated region（5＇-UTR） of thymidylate synthase（TS） gene and the susceptibility of lung cancer. Methods We conducted a case-control study with 473 lung cancer patients and 641 healthy controls in Qingdao population.The TS 5＇-UTR tandem repeat genotype was analyzed with polymerase chain reaction.Unconditional logistic regression was used to analyze the relationship between TS 5＇-UTR polymorphism and lung cancer susceptibility. Results The frequency of TS 5＇-UTR genotypes（3R/3R,2R/3R,2R/2R） was 62.2%,34.0%,and 38% in the lung cancer patients and 60.5%,37.0%,and 2.5% in the controls,respectively.Compared with TS 5＇-UTR 3R/3R genotype,2R/3R genotype showed a decreased risk of lung cancer（odds ratio=0.90,95%confidence interval：0.69-1.17）,while 2R/2R genotype showed an increased risk（OR=1.64,95%CI：0.80-3.38）.However,the results did not reach statistical significance（P0.05）.After adjusting for age,gender,smoking,alcohol use,and histological type and stage,no significant effect of the TS 5＇-UTR polymorphism was found in each subgroup. Conclusion There was no evidence for a major role of the polymorphism of TS 5＇-UTR in carcinogenesis of lung cancer by genotype alone and no obvious interaction was found between smoking,alcohol use and the polymorphism in lung cancer development.